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Amevive (Biogen Inc.)

Amevive (Biogen Inc.) - General Information

Immunosuppressive dimeric fusion protein that consists of the extracellular CD2-binding portion of the human leukocyte function antigen-3 (LFA-3) linked to the Fc (hinge, CH2 and CH3 domains) portion of human IgG1. Produced by CHO cells, mW is 91.4 kD.

 

Pharmacology of Amevive (Biogen Inc.)

Interferes with lymphocyte activation by specifically binding to the lymphocyte antigen, CD2, and inhibiting LFA-3/CD2 interaction. Activation of T lymphocytes involving the interaction between LFA-3 on antigen-presenting cells and CD2 on T lymphocytes plays a role in the pathophysiology of chronic plaque psoriasis. Also causes a reduction in subsets of CD2+ T lymphocytes as well as CD4+ and CD8+ T lymphocytes.

 

Amevive (Biogen Inc.) for patients

Patients should be informed of the need for regular monitoring of white blood cell (lymphocyte) counts during therapy and that AMEVIVE® must be administered under the supervision of a physician. Patients should also be informed that AMEVIVE® reduces lymphocyte counts, which could increase their chances of developing an infection or a malignancy. Patients should be advised to inform their physician promptly if they develop any signs of an infection or malignancy while undergoing a course of treatment with AMEVIVE®.

Female patients should also be advised to notify their physicians if they become pregnant while taking AMEVIVE® (or within 8 weeks of discontinuing AMEVIVE®) and be advised of the existence of and encouraged to enroll in the Pregnancy Registry. Call 1-866-AMEVIVE (1-866-263-8483) to enroll into the Registry.

Patients should be advised that serious liver injury has been reported in patients receiving AMEVIVE® . Patients should be advised to report to their physician persistent nausea, anorexia, fatigue, vomiting, abdominal pain, jaundice, easy bruising, dark urine or pale stools.

Laboratory Tests

CD4+ T lymphocyte counts should be monitored weekly during the 12-week dosing period and used to guide dosing. Patients should have normal CD4+ T lymphocyte counts prior to an initial or a subsequent course of treatment with AMEVIVE®. Dosing should be withheld if CD4+ T lymphocyte counts are below 250 cells/µL. AMEVIVE® should be discontinued if CD4+ T lymphocyte counts remain below 250 cells/µL for one month.

 

Amevive (Biogen Inc.) Interactions

No formal interaction studies have been performed. The duration of the period following treatment with AMEVIVE® before one should consider starting other immunosuppressive therapy has not been evaluated.

Carcinogenesis, Mutagenesis, and Fertility

In a chronic toxicity study, cynomolgus monkeys were dosed weekly for 52 weeks with intravenous alefacept at 1 mg/kg/dose or 20 mg/kg/dose. One animal in the high dose group developed a B-cell lymphoma that was detected after 28 weeks of dosing. Additional animals in both dose groups developed B-cell hyperplasia of the spleen and lymph nodes.

All animals in the study were positive for an endemic primate gammaherpes virus also known as lymphocryptovirus (LCV). Latent LCV infection is generally asymptomatic, but can lead to B-cell lymphomas when animals are immune suppressed.

In a separate study, baboons given 3 doses of alefacept at 1 mg/kg every 8 weeks were found to have centroblast proliferation in B-cell dependent areas in the germinal centers of the spleen following a 116-day washout period.

The role of AMEVIVE® in the development of the lymphoid malignancy and the hyperplasia observed in non-human primates and the relevance to humans is unknown. Immunodeficiency-associated lymphocyte disorders (plasmacytic hyperplasia, polymorphic proliferation, and B-cell lymphomas) occur in patients who have congenital or acquired immunodeficiencies including those resulting from immunosuppressive therapy.

No carcinogenicity or fertility studies were conducted.

Mutagenicity studies were conducted in vitro and in vivo; no evidence of mutagenicity was observed.

Pregnancy (Category B)

Women of childbearing potential make up a considerable segment of the patient population affected by psoriasis. Since the effect of AMEVIVE® on pregnancy and fetal development, including immune system development, is not known, health care providers are encouraged to enroll patients currently taking AMEVIVE® who become pregnant into the Biogen Pregnancy Registry by calling 1-866-AMEVIVE (1-866-263-8483).

Reproductive toxicology studies have been performed in cynomolgus monkeys at doses up to 5 mg/kg/week (about 62 times the human dose based on body weight) and have revealed no evidence of impaired fertility or harm to the fetus due to AMEVIVE®. No abortifacient or teratogenic effects were observed in cynomolgus monkeys following intravenous bolus injections of AMEVIVE® administered weekly during the period of organogenesis to gestation. AMEVIVE® underwent trans-placental passage and produced in utero exposure in the developing monkeys. In utero, serum levels of exposure in these monkeys were 23% of maternal serum levels. No evidence of fetal toxicity including adverse effects on immune system development was observed in any of these animals.

Animal reproduction studies, however, are not always predictive of human response and there are no adequate and well-controlled studies in pregnant women. Because the risk to the development of the fetal immune system and postnatal immune function in humans is unknown, AMEVIVE® should be used during pregnancy only if clearly needed. If pregnancy occurs while taking AMEVIVE®, continued use of the drug should be assessed.

Nursing Mothers

It is not known whether AMEVIVE® is excreted in human milk. Because many drugs are excreted in human milk, and because there exists the potential for serious adverse reactions in nursing infants from AMEVIVE®, a decision should be made whether to discontinue nursing while taking the drug or to discontinue the use of the drug, taking into account the importance of the drug to the mother.

Geriatric Use

Of the 1357 patients who received AMEVIVE® in clinical trials, a total of 100 patients were ≥ 65 years of age and 13 patients were ≥ 75 years of age. No differences in safety or efficacy were observed between older and younger patients, but there were not sufficient data to exclude important differences. Because the incidence of infections and certain malignancies is higher in the elderly population, in general, caution should be used in treating the elderly.

Pediatric Use

The safety and efficacy of AMEVIVE® in pediatric patients have not been studied. AMEVIVE® is not indicated for pediatric patients.

 

Amevive (Biogen Inc.) Contraindications

AMEVIVE® should not be administered to patients with known hypersensitivity to AMEVIVE® or any of its components.

 

Additional information about Amevive (Biogen Inc.)

Amevive (Biogen Inc.) Indication: For treatment of moderate to severe chronic plaque psoriasis
Mechanism Of Action: Inhibits T-lymphocyte activation and production by binding to the CD2 lymphocyte antigen.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Alefacept
Synonyms: Amevive
Drug Category: Immunomodulatory Agents; Immunosuppressive Agents
Drug Type: Biotech; Approved; Investigational
Other Brand Names containing Alefacept: Amevive (Biogen Inc.);
Absorption: Not Available
Toxicity (Overdose): Not Available
Protein Binding: Not Available
Biotransformation: Not Available
Half Life: ~270 hours
Dosage Forms of Amevive (Biogen Inc.): Powder, for solution Intramuscular
Chemical IUPAC Name: Human LFA-3/IgG1 fusion protein
Chemical Formula: C2306H3594N610O694S26
Alefacept on Wikipedia: http://en.wikipedia.org/wiki/Alefacept
Organisms Affected: Humans and other mammals